<p>Guidelines for the treatment of gastrointestinal stromal tumors (GIST) are available from several organizations and are similar in many of their recommendations, but applying them to clinical practice can be challenging and nuanced. Our featured experts discuss their approaches to the management of GIST in their own practices.</p>

For me, the management of small GIST depends on where the tumors are located and whether they are exophytic or endophytic. For exophytic GIST on the greater curvature, laparoscopic surgery can be done fairly easily and quickly. However, endophytic tumors and those near the gastroesophageal junction or pylorus are more difficult to remove. For a tumor smaller than 2 cm in diameter, I often tell patients that we can watch the tumor. However, patients often want to have the tumor taken out.

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I prefer to follow patients by computed tomography scan. Endoscopic ultrasound is a plus/minus option, and many biopsies do not yield any tissue. I think that the best way to visualize small GIST through computed tomography is by having the patient drink water approximately 10 to 15 minutes before the scan because water distends the stomach and improves visualization of small tumors.

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The length of follow-up in the GIST community seems to be variable, and I have seen patients who were discharged from follow-up after 1 to 2 years, even with decently sized tumors. It would be beneficial for clinicians to refer these patients to a specialist as early as possible, even just for an opinion, and then they can go back to their local clinicians for care.

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With respect to adjuvant therapy with imatinib, it is difficult to know what duration of treatment to use, and I am not convinced that we are improving overall survival. I say that because, while imatinib definitely delays recurrence, in my experience, when recurrence occurs, it tends to be a small amount of disease that typically responds when imatinib is restarted.

Contemporary guidelines recommend the consideration of endoscopic ultrasound for GIST tumors that are less than 2 cm. If I can adequately visualize the tumor on imaging, I do not routinely recommend endoscopic evaluation. For older patients with small tumors who decline surgery altogether, I will often follow with serial imaging alone and let tumor biology dictate when to consider systemic therapy.

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I have often struggled with the use of adjuvant therapy for patients with intermediate-risk GIST. Historically, for those with intermediate-risk disease who met the criteria for the ACOSOG Z9001 study, I would treat for 1 year and then consider discontinuing therapy. I would reserve 3 years of adjuvant imatinib therapy for patients who met “high-risk” criteria, as defined by the SSGXVIII/AIO study.

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I think that the recently published IMADGIST study exploring the use of adjuvant imatinib for 6 years compared with 3 years has helped in the intermediate-risk patient population. It showed a disease-free survival benefit with the use of adjuvant imatinib therapy in patients with at least a 35% risk of recurrence, whereas previous studies focused on patients at higher risk.

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With respect to neoadjuvant therapy, if someone had a PDGFRA D842V–mutated tumor, I would consider using avapritinib in the neoadjuvant setting the same way I would consider using imatinib for imatinib-sensitive disease. Otherwise, I would not routinely consider other therapies for neoadjuvant treatment outside of a clinical trial, with the exception of a patient who is in need of neoadjuvant therapy and is intolerant to imatinib.

Micro-GIST are very common, and the decision of whether to monitor or resect depends on factors including the patient’s age, comorbidities, and mutation status. If micro-GIST have been excised during surgery, that is the end of the story. If they are still in place, I might have the patient visually scoped for a period. If the GIST are not doing anything, then the patient does not need additional follow-up. A German autopsy series that is often quoted found micro-GIST in 22.5% of autopsies, so these are very common.

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In terms of adjuvant therapy, we all struggle with deciding what to do for patients with intermediate-risk GIST, as it is a bit nuanced. In contrast, the treatment of patients with very high-risk and very low-risk GIST is pretty clear. I think that some patients with intermediate-risk disease need to be treated, while others probably do not. I tend to treat if the GIST are at the upper end of intermediate risk but usually do not if they are at the lower end, unless the tumors are in the small intestine, where I think the risk is underestimated. Life expectancy also plays a role, as does whether the patient has KIT or PDGFRA mutations. If a patient’s tumors do not have an imatinib-sensitive mutation, I might not treat. Ultimately, however, I provide patients with information, get an idea of what their goals are, and let them know that it is their decision.

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Since approximately 10% of patients do not have imatinib-sensitive mutations and may not have any benefit from imatinib, mutation testing is very important. Unfortunately, patients with GIST frequently do not receive mutation testing in the adjuvant setting.